University of Texas Medical Branch

About: University of Texas Medical Branch is a education organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Population & Virus. The organization has 22033 authors who have published 38268 publications receiving 1517502 citations. The organization is also known as: The University of Texas Medical Branch at Galveston & UTMB.

A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection

Abstract: Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.

Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression

Abstract: The timing of type I interferon signalling determines the disease course of SIV infection. Type I interferon (IFN-I) is shown here to have dual effects in rhesus macaques exposed to simian immunodeficiency virus (SIV): it is beneficial at the onset of infection but as infection progresses it becomes detrimental. IFN signaling was manipulated in two ways. IFN-I receptor blockade results in increased plasma viraemia, accelerated CD4 T cell loss and progression to AIDS. In contrast, IFN-α2a administration prior to high-dose intrarectal SIV challenge increases resistance to systemic infection. However, continued IFN-α2a treatment induces IFN-I desensitization and facilitates SIV infection. Overall, the benefits of early antiviral activity appear to outweigh the detrimental effects of immune activation during acute SIV infection. Inflammation in HIV infection is predictive of non-AIDS morbidity and death1, higher set point plasma virus load2 and virus acquisition3; thus, therapeutic agents are in development to reduce its causes and consequences. However, inflammation may simultaneously confer both detrimental and beneficial effects. This dichotomy is particularly applicable to type I interferons (IFN-I) which, while contributing to innate control of infection4,5,6,7,8,9,10, also provide target cells for the virus during acute infection, impair CD4 T-cell recovery, and are associated with disease progression6,7,11,12,13,14,15,16,17,18,19. Here we manipulated IFN-I signalling in rhesus macaques (Macaca mulatta) during simian immunodeficiency virus (SIV) transmission and acute infection with two complementary in vivo interventions. We show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation. In contrast, IFN-α2a administration initially upregulated expression of antiviral genes and prevented systemic infection. However, continued IFN-α2a treatment induced IFN-I desensitization and decreased antiviral gene expression, enabling infection with increased SIV reservoir size and accelerated CD4 T-cell loss. Thus, the timing of IFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation. Yet, the clinical consequences of manipulation of IFN signalling are difficult to predict in vivo and therapeutic interventions in human studies should be approached with caution.

Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction

Abstract: Muscle protein synthesis and breakdown and amino acid transport were measured in 7 healthy young (30 ± 2 yr) and 8 healthy elderly (71 ± 2 yr) volunteers in the postabsorptive state and during the ...

Cutaneous sensory receptors in the rat foot

Abstract: 1. A total of 574 cutaneous afferent units in the sural and plantar nerves supplying the skin of the rat foot was examined: 399 A beta-units, 55 A delta-units, and 120 C-units. Their receptive-field (RF) properties were similar to those described in other mammals. However, the receptor type composition of units was different between the two nerves. 2. The sural A beta-fiber sample (n = 160) consisted of G-hair (41%), field (11%), rapidly adapting (RA; 6%), slowly adapting type I (SA-I; 7%), and type II (SA-II; 35%) mechanoreceptors. The plantar A beta-fiber sample (n = 239) was composed of G-hair (3%), RA (35%), SA-I (30%), SA-II (24%), and Pacinian corpuscle (PC; 8%) mechanoreceptors. 3. The RFs of SA-II units were located on both hairy and glabrous skin overlying the foot joints. Many of the SA-II units responded to movement of the foot joints. The RFs of both SA-I and RA units were small in size and located in high density on the toe tips and footpads. PC units were very sensitive to vibration and had extremely large RFs as in other species, although they were rare and found only in the plantar nerve. Field units were similar to SA-II units in response properties and RF distribution. 4. The sural A delta-fiber sample (n = 44) included nociceptors (68%), D-hair (27%), and cold (5%) receptors. All sampled plantar A delta-fibers (n = 11) were nociceptors. Of A delta-nociceptor units, A delta-mechanical nociceptors (73%) were dominant. 5. The sural C-fiber sample (n = 85) included nociceptors (44%), C-mechanoreceptors (33%), and cold receptors (21%). The plantar C-fiber sample (n = 35) included nociceptors (77%) and cold receptors (23%). No warm units were found among either the sural or plantar nerve fibers. Of C-nociceptors, C-mechanoheat nociceptors (80%) were dominant. 6. The results indicate that all well-known types of cutaneous receptors, except warm receptors, exist in the foot skin of the rat. On the basis of the fact that RFs of RA and SA-I units are in high density on the toe tips and footpads, it is suggested that those regions may have a spatial discriminating capacity. It is also suggested that SA-II receptors may play a role in proprioception, because they have RFs on the skin over foot joints and respond to joint movement.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracellular Ca2+ activates a fast voltage-sensitive K+ current in vertebrate sympathetic neurones.

Abstract: Many neurones, when depolarized, exhibit two components of outward K+ current—the voltage-sensitive delayed rectifier current originally described in squid axons by Hodgkin and Huxley1, and an additional current triggered by the entry of Ca2+ ions2. These two currents have been termed IK and IC, respectively3. Previous experiments have indicated that both forms of K+ current are also present in vertebrate sympathetic neurones4–6. We have now studied the properties of IC in bullfrog sympathetic neurones, uncontaminated with IK, by injecting Ca2+ ions into the cells and measuring the resultant outward currents under voltage-clamp, in the manner previously used for large molluscan neurones7,8. We find three interesting properties of IC in these vertebrate neurones. First, it shows strong voltage sensitivity independent of the voltage sensitivity of the Ca2+ channels (which have been bypassed by the injection technique). Second, IC activates and deactivates very rapidly (τC≤20 ms at 0 mV), with stepped changes in membrane potential. Current fluctuation analysis and patch-clamp records of single-channel currents yielded evidence for appropriate short-lifetime ionic channels with a maximum conductance of ∼100 pS. Finally IC in ganglion cells is highly sensitive to external tetraethylammonium. We deduce that in these neurones IC is a fast current which can contribute a substantial fraction to the repolarizing current during an action potential.